Sensitive detection of the presence of a target substance is an important goal recognized by both science and industry. The target substance may be a chemical or biological entity. Often the target substance occurs in such small quantities that accurate detection is frustrated by the sensitivity limitations of the detector.
Surface plasmon resonance (SPR) biosensor systems have been developed which enable measurement of chemical and biological substances. Such devices operate on the principal that energy carried by waves of light photons can be transferred to electrons in a metal. The wavelength of light at which the energy transfer occurs is a function of the metal at the interface and the environment encompassing the metal. The maximum energy is transferred from the photons to the electrons at the resonance frequency, and thus, by monitoring the light reflected by the metal surface, it is possible to determine the resonant frequency. In particular, the light reflected by the metal surface is at a minimum at the resonant frequency. Typically, in SPR systems, the angle of minimum reflection is usually used as an indication of the plasmon resonance. At the interface of the metal and a dielectric, the electrons are excited which creates an electromagnetic wave extending a short distance above and below the interface. Consequently, a change in the environment at the interface is detectable as a change in the wavelength of the resonant frequency.
The principals of SPR are used for detecting the refractive index properties of a substance in one type of biosensor system. In particular, a change in the refractive index, caused, for example, by an antigen binding to an antibody, is manifested by a change in the resonant frequency.
In practice, however, SPR biosensors have limited utility. For example, the metal at the interface is often gold or silver, and thus, any elements that react with the metal may yield erroneous results. Also, the sensitivity of SPR biosensors is inadequate for some applications. In addition, the apparatus is often too large for practical field use. Typically, SPR biosensors require large samples, often measured in microliter or larger quantities.
A fibre-optic sensor is discussed in Dahne C. Sutherland R M, Place J F, Ringrose AS. “Detection of antibody-antigen reactions at a glass-liquid interface: a novel fibre-optic sensor concept.” Proceedings of Spie—the International Society for Optical Engineering, vol. 514, 1984, pp. 75-9 (hereinafter “Dahne”). Dahne discusses detecting in-line fluorescence resulting from evanescent waves internally guided through a waveguide. The waveguide, a standard PCS fiber with 0.6 micrometers core diameter, passes through a cylindrical flow cell in which the sample solution passes. Like SPR biosensors, Dahne appears to require a relatively large quantity of sample solution since the waveguide operates in a bath of the solution.
Other techniques of detecting the presence of a particular chemical composition have included staining or labeling. For example, genotyping efforts have included radioisotope labeling. Recognized disadvantages associated with the use of radioactivity include costs, hazards associated with radioactive materials, and undesirable delays associated with such techniques.
For the reasons stated above, and for other reasons stated below which will become apparent to those skilled in the art upon reading and understanding the present specification, there is a need in the art for a highly sensitive detection system and method that allows for detection of biological or chemical material.